128 research outputs found
Self-consistent field convergence for proteins:a comparison of full and localized-molecular-orbital schemes
No full textApplying Computational Methods in the Study of Biomolecular Systems: the Recognition Mechanism of DNA Repair Enzyme Fpg
No full textStony Brook University Libraries.
Department of Chemistry,
Lawrence Martin (Dean of Graduate School), Carlos L. Simmerling (Associated Professor, Department of Chemistry), Orlando Scharer (Associated Professor, Department of Chemistry), Fernando O. Raineri (Adjunct Assistant Professor, Department of Chemistry), Arthur P. Grollman (Distinguished Professor, Pharmacological Sciences Evelyn G. Glick Professor of Experimental Medicine Director: Laboratory for Chemical Biology Stony Brook University)
Blinded Prediction of Protein-Ligand Binding Affinity Using Amber Thermodynamic Integration for the 2018 D3R Grand Challenge 4
No full textIn the framework of the 2018 Drug Design Data Resource (D3R)
grand challenge 4, blinded predictions on relative binding free energy were
performed for a set of 39 ligands of the Cathepsin S. We leveraged the GPU-accelerated
thermodynamic integration (GTI) of Amber 18 to advance our computational
prediction. When our entry was compared to experimental results, good
correlation was observed (Kendall’s τ: 0.62, Spearman’s ρ: 0.80 and Pearson’s R:
0.82), with the highest correlation to experiment among all submissions. We designing a parallelized transformation map that placed ligands into
several groups based on common alchemical substructures; TI transformations were
carried out for each ligand to the relevant substructure, and between
substructures. Our calculations were all conducted using the linear potential
scaling scheme in Amber TI because we believe the softcore potential/dual
topology approach implemented in current Amber TI is highly fault-prone. The
issue was illustrated by using two examples in which typical preparation for
the dual topology approach of Amber TI fails. Overall, the high accuracy of our
prediction is a result of recent advances in force fields (ff14SB and GAFF), as
well as rapid calculation of ensemble averages enabled by the GPU
implementation of Amber. The success in a blinded prediction strongly suggests
that alchemical free energy calculation in Amber is a promising tool for future
commercial drug design.</p
Study of Factors Affecting Amylin Fibril Formation and the Characterization of a Protein which Prevents Amyloidogenesis
No full textStony Brook University Libraries.
SBU Graduate School in Chemistry.
Lawrence Martin (Dean of Graduate School), Daniel P. Raleigh, Thesis Advisor
Professor at Department of Chemistry, Stony Brook, Peter J. Tonge, Chairperson of Defense
Professor at Department of Chemistry, Stony Brook, Carlos Simmerling, Third Member
Associate Professor at Department of Chemistry, Stony Brook, Thomas P. Sakmar, Fourth Member
Richard M, and Isabel P. Furlaud Professor, Rockefeller University, Suzanne Scarlata, Outside Member
Professor at Department of Physiology and Biophysics, Stony Brook
Study of Biologically Relevant Phenomena Using Small Peptide Models
No full textStony Brook University Libraries.
SBU Graduate School in Chemistry.
Lawrence Martin (Dean of Graduate School), Carlos L. Simmerling – Dissertation Advisor
Associated Professor, Department of Chemistry, Daniel P. Raleigh – Chairperson of Defense
Professor, Department of Chemistry, David M. Hanson – Third Member
Professor, Department of Chemistry, Alexey Onufriev – Outside Member
Associated Professor, Departments of Computer Science and Physics, Virginia Tech
Studies of the Folding and Stability of the Villin Headpiece Subdomain
No full textStony Brook University Libraries.
SBU Graduate School in Chemistry.
Lawrence Martin (Dean of Graduate School), Daniel P. Raleigh, Ph. D., Advisor
Department of Chemistry, Stony Brook University, Nicole S. Sampson, Ph. D., Chairperson
Department of Chemistry, Stony Brook University, Carlos Simmerling, Ph. D., Third Member
Department of Chemistry, Stony Brook University, Carlos de los Santos, Ph. D., Outside Member
Department of Pharmacology, Stony Brook University
Folding of α-Helical Proteins and Protein Design Using Non-coded Amino Acids
No full textStony Brook University Libraries.
SBU Graduate School in Chemistry.
Lawrence Martin (Dean of Graduate School), Daniel P. Raleigh, Ph. D., Advisor
Department of Chemistry, Stony Brook University, Peter J. Tonge, Ph. D., Chairperson
Department of Chemistry, Stony Brook University, Carlos Simmerling, Ph. D., Third Member
Department of Chemistry, Stony Brook University, Carlos De Los Santos, Ph. D., Outside Member
Department of Pharmacology, Stony Brook University
The Dynamic Nature of the Folded and Unfolded States of the Villin Headpiece Helical Subdomain
No full textStony Brook University Libraries. Biochemistry and Structural Biology. Lawrence Martin (Dean of Graduate School), Carlos Simmerling, Ph. D., Advisor
Department of Chemistry, Stony Brook University, Daniel P. Raleigh, Ph. D., Advisor
Department of Chemistry, Stony Brook University, Steven O. Smith, Ph. D., Chair
Department of Biochemistry and Cell Biology, Stony Brook University, Robert C. Rizzo, Ph. D., Third Member
Department of Applied Mathematics and Statistics, Stony Brook University, Marivi Fernandez-Serra, Ph. D., Outside Member
Department of Physics and Astronomy, Stony Brook University
Recommended from our members
Dissecting the Energetics of Intrinsically Disordered Proteins via a Hybrid Experimental and Computational Approach
No full textIntrinsically disordered proteins (IDPs) play important roles in biology, but little is known about the energetics of their inter-residue interactions. Methods that have been successfully applied to analyze the energetics of globular proteins are not applicable to the fluctuating partially ordered ensembles populated by IDPs. A combined computational experimental strategy is introduced for analyzing the energetic role of individual residues in the free state of IDPs. The approach combines experimental measurements of the binding of wild-type and mutant IDPs to their partners with alchemical free energy calculations of the structured complexes. These data allow quantitative information to be deduced about the free state via a thermodynamic cycle. The approach is validated by the analysis of the effects of mutations upon the binding free energy of the ovomucoid inhibitor third binding domain to its partners and is applied to the C-terminal domain of the measles virus nucleoprotein, a 125-residue IDP involved in the RNA transcription and replication of measles virus. The analysis reveals significant inter-residue interactions in the unbound IDP and suggests a biological role for them. The work demonstrates that advances in force fields and computational hardware have now led to the point where it is possible to develop methods, which integrate experimental and computational techniques to reveal insights that cannot be studied using either technique alone
Dissecting the Energetics of Intrinsically Disordered Proteins via a Hybrid Experimental and Computational Approach
No full text- …
